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THOUSAND OAKS, Calif., Sept. 5, 2021 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced new data from the pivotal NAVIGATOR Phase 3 trial demonstrating that tezepelumab reduced exacerbations and improved lung function and nasal symptoms in patients with severe, uncontrolled asthma and comorbid nasal polyps.1 Tezepelumab is a potential first-in-class treatment that acts at the top of the inflammatory cascade by targeting thymic stromal lymphopoietin (TSLP), an epithelial cytokine, and has the potential to treat a broad population of patients with severe asthma.2,3 Tezepelumab is being developed by Amgen in collaboration with AstraZeneca.
The pre-specified exploratory analysis evaluated the effect of tezepelumab in NAVIGATOR patients with or without reported nasal polyps (NP+ or NP−) in the past two years. The analysis showed tezepelumab achieved an 86% reduction in the annualized asthma exacerbation rate (AAER) in NP+ patients (95% CI: 70, 93) and 52% (95% CI: 42, 61) in NP− patients over 52 weeks, compared to placebo when added to standard of care (SoC).1
Tezepelumab improved lung function at week 52 in both groups of patients with an increase in pre-bronchodilator forced expiratory volume in one second (FEV1) of 0.20 L (95% CI: 0.02, 0.37) and 0.13 L (95% CI: 0.08, 0.18) versus placebo in NP+ and NP− patients, respectively.1 Tezepelumab also achieved a clinically relevant improvement in nasal polyp symptoms at week 52, as measured by the Sinonasal Outcome Test (SNOT-22), reducing the SNOT-22 score in NP+ patients by 9.6 points (95% CI: 0.9, 18.2) versus placebo.1,4 The adjusted mean score reductions from baseline for tezepelumab and placebo were 20.10 points (SE: 3.07) and 10.55 points (SE: 2.94). Baseline mean (sd) SNOT-22 score was 49.4 (21.5) and 47.8 (19.0) for tezepelumab and placebo, respectively.1
"This new analysis from NAVIGATOR is exciting for the up to one in five severe asthma patients who have comorbid nasal polyps," said Professor Andrew Menzies-Gow, director of the Lung Division, Royal Brompton Hospital, London, UK, the principal investigator of the NAVIGATOR trial. "The analysis shows tezepelumab's ability to reduce exacerbations, improve lung function and reduce the symptoms of nasal polyps in this comorbid population who are typically more prone to asthma attacks, have an increased likelihood of airway obstruction, and may have a worse quality of life."
"We're thrilled to see significant reductions in exacerbations experienced by patients with severe asthma and comorbid nasal polyps as noted within the latest analysis of NAVIGATOR data," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "These results further strengthen our confidence in tezepelumab's potential to address a significant unmet need across a broad population of patients with severe asthma, including those with comorbid nasal polyps. We look forward to bringing this potentially transformative treatment to patients soon."
These findings were presented at the European Respiratory Society (ERS) International Congress 2021 between September 5-8. There were no clinically meaningful differences in safety results between the tezepelumab and placebo groups in the NAVIGATOR trial. The most frequently reported adverse events with tezepelumab were nasopharyngitis, upper respiratory tract infection and headache.5
Results from the NAVIGATOR Phase 3 trial were published in the New England Journal of Medicine in May 2021.5 A Phase 3 clinical trial, WAYPOINT, has been initiated to explore the efficacy and safety of tezepelumab in adults with severe, chronic rhinosinusitis with nasal polyps.6
About Severe AsthmaGlobally, there are approximately 2.5 million patients with severe asthma who are uncontrolled or biologic eligible, with approximately 1 million in the U.S. Many patients with severe asthma have an inadequate response to currently available biologics and oral corticosteroids and thus fail to achieve asthma control.7,8,9 Uncontrolled asthma occurs when symptoms persist despite treatment. Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life. 7,8,9 Patients with severe uncontrolled asthma have twice the risk of asthma-related hospitalizations.10,11 There is also a significant socio-economic burden with these severe uncontrolled asthma patients accounting for 50% of asthma-related costs.12
Multiple inflammatory pathways are involved in the pathogenesis of asthma.13-15 Eosinophilic asthma, and more broadly, T2 inflammation-driven asthma, accounts for about two-thirds of patients with severe asthma.15 These patients are typically characterized as having elevated levels of inflammatory biomarkers, including blood eosinophils, serum IgE and fractional exhaled nitric oxide (FeNO).16,17 However, many patients do not fit the criteria for eosinophilic or allergic asthma, may have unclear or multiple drivers of inflammation, and may not qualify for or respond well to a current biologic medicine.17
Nasal polyps are benign growths that arise from the mucosa of the nose and paranasal sinuses.18 Up to 22% of severe asthma patients have comorbid nasal polyps.19 Nasal polyps can block nasal passages and lead to breathing problems, reduction in the sense of smell, nasal discharge, sleep disturbance and other adverse effects on quality of life.20-22
About the NAVIGATOR and the PATHFINDER Clinical Trial ProgramBuilding on the Phase 2b PATHWAY trial, the Phase 3 PATHFINDER program included two trials, NAVIGATOR5,23 and SOURCE.24,25 The program includes additional planned mechanistic and long-term safety trials.26 In addition, a Phase 3 clinical trial, WAYPOINT, has been initiated to explore the efficacy and safety of tezepelumab in adults with severe, chronic rhinosinusitis with nasal polyps.6
NAVIGATOR is a Phase 3, randomized, double-blinded, placebo-controlled trial in 1,061 adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who were receiving treatment with medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication with or without OCS. Of the 1,061 randomized patients, 1,059 received either tezepelumab 210 mg (n=528) or placebo (n=531). In total for this pre-specified exploratory analysis, 83 patients had NP in the past 2 years (tezepelumab 210 mg, n=42; placebo, n=41) and 976 did not (tezepelumab 210 mg, n=486; placebo, n=490). NAVIGATOR met the primary endpoint with tezepelumab added to SoC demonstrating a statistically significant and clinically meaningful reduction in the AAER over 52 weeks in the overall patient population, compared to placebo added to SoC. The trial also met the primary endpoint in the subgroup of patients with baseline eosinophil counts less than 300 cells per microliter, with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in AAER in that patient population. Similar reductions in AAER were observed in the subgroup of patients with baseline eosinophil counts less than 150 cells per microliter.26,27
NAVIGATOR primary endpoints5 | ||||
Endpoint | Timepoint | Annual Exacerbation Rate | Results Tezepelumab added to SoC vs placebo added to SoC | |
Tezepelumab | Placebo | |||
AAER – overall patient population | Over 52 weeks | 0.93 (95% CI: 0.80, 1.07) | 2.10 (95% CI: 1.84, 2.39) | 56% reduction (95% CI: 47, 63; p
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